Recently, cancer treatment with a combination of radiation and anticancer drug has been widely applied to enhance cell death in solid tumor cells. A purine analog 8-amino-adenosine is converted into its triphosphate form, 8-amino-ATP, after uptake by cells. Intracellular accumulation of 8-amino-ATP is reported to induce the depletion of ATP level and the inhibition of RNA/DNA synthesis. In this study, we examined whether 8-amino-adenosine has an ability to enhance radiation-induced reproductive cell death and apoptosis. Human lung adenocarcinoma A549 cells were treated without or with 8-amino-adenosine and irradiated. Reproductive cell death was assessed by clonogenic assay and apoptotic cells were evaluated by propidium iodide staining. Expression of apoptosis-related proteins was examined by western blot analysis. 8-Amino-adenosine significantly increased reproductive cell death as well as apoptosis induced by X-irradiation. When peptide inhibitors against caspase-3, -8, -9 were utilized to evaluate the involvement of caspases in this increase of apoptosis, all inhibitors suppressed the enhancement of radiation-induced apoptosis. This result suggested that not only mitochondria-mediated apoptotic signal transduction pathways but also death receptor-mediated one, were involved in this radiation-induced apoptosis in the presence of 8-amino-adenosine. In addition, 8-amino-adenosine inhibited the expression of an anti-apoptotic protein, survivin, suggesting that this inhibition could contribute to the enhancement of radiation-induced apoptosis. We are currently examining if 8-amino-ATP instead of endogenous ATP acts as a promoting factor of apoptosis.